An in-depth understanding of genetic and biochemical regulation in mammalian cells is necessary to the understanding of maturation, malignancy, and the aging process. The regulation of two critical biochemical pathways, those of purine and pyrimidine biosynthesis, will be studied in Chinese hamster cells grown in culture in order to obtain this fundamental knowledge. This will be done by the isolation and biochemical and genetic characterization of Chinese hamster cell mutants defective in purine and in pyrimidine biosynthesis. Complementation analysis, assignment of the genes in the biosynthetic pathways to appropriate human chromosomes, and linkage analysis on the human chromosomes, will be carried out by construction of appropriate hamster-hamster and hamster-human hybrid cells. The nature of the biochemical defect in each complementation group will be determined. Interaction of various genetic mutations will be studied in appropriate hybrids. Attempts will be made to determine the exact nature of the genetic lesion in each mutant class. The information gained in understanding the genetic and biochemical regulation of these two important pathways in somatic mammalian cells should be useful in the understanding of human normal and abnormal developmental processes, including aging and malignancy.